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Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
The extremely poor prognosis of patients affected by glioblastoma (GBM, grade IV glioma) prompts the search for new and more effective therapies. In this regard, drug repurposing or repositioning can represent a safe, swift, and inexpensive way to bring novel pharmacological approaches from bench to...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952964/ https://www.ncbi.nlm.nih.gov/pubmed/33718225 http://dx.doi.org/10.3389/fonc.2021.635472 |
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author | Matteoni, Silvia Matarrese, Paola Ascione, Barbara Buccarelli, Mariachiara Ricci-Vitiani, Lucia Pallini, Roberto Villani, Veronica Pace, Andrea Paggi, Marco G. Abbruzzese, Claudia |
author_facet | Matteoni, Silvia Matarrese, Paola Ascione, Barbara Buccarelli, Mariachiara Ricci-Vitiani, Lucia Pallini, Roberto Villani, Veronica Pace, Andrea Paggi, Marco G. Abbruzzese, Claudia |
author_sort | Matteoni, Silvia |
collection | PubMed |
description | The extremely poor prognosis of patients affected by glioblastoma (GBM, grade IV glioma) prompts the search for new and more effective therapies. In this regard, drug repurposing or repositioning can represent a safe, swift, and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication used since six decades for the therapy of psychiatric disorders, shows in vitro several features that make it eligible for repositioning in cancer therapy. Using six GBM cell lines, three of which growing as patient-derived neurospheres and displaying stem-like properties, we found that chlorpromazine was able to inhibit viability in an apoptosis-independent way, induce hyperdiploidy, reduce cloning efficiency as well as neurosphere formation and downregulate the expression of stemness genes in all these cell lines. Notably, chlorpromazine synergized with temozolomide, the first-line therapeutic in GBM patients, in hindering GBM cell viability, and both drugs strongly cooperated in reducing cloning efficiency and inducing cell death in vitro for all the GBM cell lines assayed. These results prompted us to start a Phase II clinical trial on GBM patients (EudraCT # 2019-001988-75; ClinicalTrials.gov Identifier: NCT04224441) by adding chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol. |
format | Online Article Text |
id | pubmed-7952964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79529642021-03-13 Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro Matteoni, Silvia Matarrese, Paola Ascione, Barbara Buccarelli, Mariachiara Ricci-Vitiani, Lucia Pallini, Roberto Villani, Veronica Pace, Andrea Paggi, Marco G. Abbruzzese, Claudia Front Oncol Oncology The extremely poor prognosis of patients affected by glioblastoma (GBM, grade IV glioma) prompts the search for new and more effective therapies. In this regard, drug repurposing or repositioning can represent a safe, swift, and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication used since six decades for the therapy of psychiatric disorders, shows in vitro several features that make it eligible for repositioning in cancer therapy. Using six GBM cell lines, three of which growing as patient-derived neurospheres and displaying stem-like properties, we found that chlorpromazine was able to inhibit viability in an apoptosis-independent way, induce hyperdiploidy, reduce cloning efficiency as well as neurosphere formation and downregulate the expression of stemness genes in all these cell lines. Notably, chlorpromazine synergized with temozolomide, the first-line therapeutic in GBM patients, in hindering GBM cell viability, and both drugs strongly cooperated in reducing cloning efficiency and inducing cell death in vitro for all the GBM cell lines assayed. These results prompted us to start a Phase II clinical trial on GBM patients (EudraCT # 2019-001988-75; ClinicalTrials.gov Identifier: NCT04224441) by adding chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol. Frontiers Media S.A. 2021-02-26 /pmc/articles/PMC7952964/ /pubmed/33718225 http://dx.doi.org/10.3389/fonc.2021.635472 Text en Copyright © 2021 Matteoni, Matarrese, Ascione, Buccarelli, Ricci-Vitiani, Pallini, Villani, Pace, Paggi and Abbruzzese http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Matteoni, Silvia Matarrese, Paola Ascione, Barbara Buccarelli, Mariachiara Ricci-Vitiani, Lucia Pallini, Roberto Villani, Veronica Pace, Andrea Paggi, Marco G. Abbruzzese, Claudia Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro |
title | Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
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title_full | Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
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title_fullStr | Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
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title_full_unstemmed | Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
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title_short | Anticancer Properties of the Antipsychotic Drug Chlorpromazine and Its Synergism With Temozolomide in Restraining Human Glioblastoma Proliferation In Vitro
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title_sort | anticancer properties of the antipsychotic drug chlorpromazine and its synergism with temozolomide in restraining human glioblastoma proliferation in vitro |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952964/ https://www.ncbi.nlm.nih.gov/pubmed/33718225 http://dx.doi.org/10.3389/fonc.2021.635472 |
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